Gordeuk V, Thuma P, Brittenham G, McLaren C, Parry D, Backenstose A, Biemba G, Msiska R, Holmes L, McKinley E
Case Western Reserve University School of Medicine, Cleveland, OH.
N Engl J Med. 1992 Nov 19;327(21):1473-7. doi: 10.1056/NEJM199211193272101.
Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy.
To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis.
The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52).
Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria.
脑型疟疾是儿童恶性疟原虫感染的一种严重并发症，尽管进行了抗疟治疗，其死亡率仍为15%至50%。
为了确定铁螯合疗法与奎宁疗法联合使用是否能加快意识恢复，我们对83名患有脑型疟疾的赞比亚儿童进行了一项关于铁螯合剂去铁胺的随机、双盲、安慰剂对照试验。入选患者必须年龄小于6岁，患有恶性疟原虫血症，脑脊液正常且无细菌感染证据，并且处于昏迷状态且无法唤醒。在使用奎宁和磺胺多辛 - 乙胺嘧啶的标准治疗基础上加用去铁胺（每天每千克体重100毫克，静脉输注72小时）或安慰剂。采用Cox比例风险回归分析来检查完全意识恢复时间、寄生虫清除时间和死亡率。
42名接受去铁胺治疗的患者中完全意识恢复率是41名接受安慰剂治疗患者的1.3倍（95%置信区间为0.7至2.3）；去铁胺组的中位恢复时间为20.2小时，安慰剂组为43.1小时（P = 0.38）。在50名深度昏迷患者中，去铁胺使完全意识恢复率提高了2.2倍（95%置信区间为1.1至4.7），将中位恢复时间从68.2小时缩短至24.1小时（P = 0.03）。在69名可获得寄生虫清除数据的患者中，去铁胺的清除率是安慰剂的2.0倍（95%置信区间为1.2至3.6）。在所有83名患者中，去铁胺组的死亡率为17%，安慰剂组为22%（P = 0.52）。
铁螯合疗法可能会加快脑型疟疾中疟原虫血症的清除，并促进深度昏迷患者的恢复。
